The zinc oxide nanoparticles (ZnO-NPs) being widely employed in several industries and consumer products, are raising concerns about their safety on aquatic biota and human health. This study aims to investigate the possible toxicological effects of ZnO-NPs through a combined in vivo and in silico approach. Zebrafish embryos were exposed to several ZnO-NPs concentrations and morphological alterations and lipid peroxidation (MDA) were investigated. Furthermore, molecular docking simulations were applied to study the intermolecular interactions of ZnO-NPs against critical embryonic proteins namely zebrafish hatching enzyme1 (ZHE1) as well as the superoxide dismutase (SOD1). Treatment with ZnO-NPs resulted in an increase in MDA concentration and a decrease in antioxidant enzyme levels. Besides a significant decrease in mRNA expression of key enzymes of ROS detoxification genes, a modulation of inflammatory genes with a low downregulation of tnf-α, and an upregulation of il-1β were observed. Docking study suggests that the delayed hatching and increased cellular oxidative stress in zebrafish embryos may occur through a synergistic mechanism based on the ZnO-NP-dependent inhibition of ZHE1 and SOD1 enzymes. The integration of in vivo assessments with in silico computational modeling provided a more comprehensive evaluation of potential physiological risks in zebrafish embryos associated with nanomaterial exposure.

Oxysterols have long been considered as simple by-products of cholesterol metabolism, but they are now fully designed as bioactive lipids that exert their multiple effects through their binding to several receptors, representing endogenous mediators potentially involved in several metabolic diseases. There is also a growing concern that metabolic disorders may be linked with exposure to endocrine-disrupting chemicals (EDCs). To date, there are no studies aimed to link EDCs exposure to oxysterols perturbation—neither in vivo nor in vitro studies. The present research aimed to evaluate the differences in oxysterols levels following exposure to two metabolism disrupting chemicals (propylparaben (PP) and triclocarban (TCC)) in the zebrafish model using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Following exposure to PP and TCC, there were no significant changes in total and individual oxysterols compared with the control group; however, some interesting differences were noticed: 24-OH was detected only in treated zebrafish embryos, as well as the concentrations of 27-OH, which followed a different distribution, with an increase in TCC treated embryos and a reduction in zebrafish embryos exposed to PP at 24 h post-fertilization (hpf). The results of the present study prompt the hypothesis that EDCs can modulate the oxysterol profile in the zebrafish model and that these variations could be potentially involved in the toxicity mechanism of these emerging contaminants.

Human chemical carcinogenesis is a multistage process where chemicals or their metabolites cause irreversible changes in normal cell physiology, eventually leading to uncontrolled proliferation, transforming a normal cell into a cancerous one. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation, and immune responses. Its aberrant activation triggers tumor progression by promoting the expression of oncogenic genes; thus, STAT3 is classified as an oncoprotein. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to a wide variety of chemicals, including carcinogens like dioxins, inducing genes associated with detoxification, proliferation, and immune regulation. Recent reports show that AhR plays a critical role in cancer development and maintenance. AhR may interact with signaling pathways, like the STAT3 pathway, which mediates the carcinogenic effects of several pollutants. Various chemical agents, such as industrial waste and hydrocarbon compounds, can alter the expression or signaling activity of AhR and STAT3 pathways, leading to different types of cancers. Understanding the complex STAT3-AhR network in the regulation of chemical carcinogenesis could open new avenues for cancer prevention or treatment, particularly in personalized medicine, aiming to improve life expectancy and achieving a complete cure.

Glyphosate (Gly), a systemic and non-selective post-emergence herbicide used worldwide, has emerged as a pollutant. However, its toxic effects are debated by regulatory authorities. In addition, in the aquatic environment, often the presence of pollutants is associated with a hypoxia condition that could change their toxicological effects. We used zebrafish embryos to evaluate the toxic effects of Gly and its mechanisms in a hypoxic condition chemically induced by cobalt chloride (CoCl₂). We found that Gly induced toxicity in a time and concentration-dependent manner. The toxicity of Gly was determined at 96 hours post fertilization as a lethal concentration (LC), and LC₁₀, LC₂₀, and LC₅₀ values were 85.7, 97, and 122.9 mg/L, respectively. When Gly was combined with CoCl₂ the toxicological endpoints were lower than values referred to the Gly alone indicating the worse effects of chemical hypoxia on Gly toxicity. Histological observations were performed at 25, 50, 75, and 100 mg/L for Gly both alone and in combination with 10 mM CoCl₂. Fisher's exact test showed significant differences in the presence of hepatic and gut inflammation at 75 and 100 mg/L of Gly both alone and in combination with CoCl₂. To deeply investigate the effects of hypoxia on Gly toxicity we decided to test the lowest dose of Gly, 50 mg/L, alone or in combination with CoCl₂ 10 mM on liver glycogen storage and oxidative stress. Again the results obtained indicate the worse effects of chemical hypoxia on Gly toxicity. Thus Gly toxicity could be reconsidered in light of the damage it causes to the liver and intestines and its effect in combination with factors that induce chemical hypoxia.

The extensive use of pesticides in agriculture significantly enhances crop yields and pest control. However, it also raises concerns regarding environmental and human health impacts. Children are particularly vulnerable to health effects of pesticide exposure, especially for neurological development and reproductive health. This study aims to evaluate the association between dietary pesticide exposure and idiopathic premature thelarche in girls living in an intensive agricultural area in central Italy. Using a case-control study, pesticide residues exposure was assessed through dietary intake of local food and by urinary levels. Results showed that the dietary intake of some pesticides from fruit and vegetables was higher in affected girls than healthy controls, although not significantly associated with idiopathic premature thelarche risk. Moreover, low health risk was obtained for cumulative dietary exposure. Despite this, further efforts are needed to reduce pesticide residues in food due to their potential endocrine disrupting properties, considering that diet may be one of several sources of exposure, especially in rural areas.